Characteristics and Dosing Patterns of Tirzepatide Users with Type 2 Diabetes in the United States

Abstract

Introduction

The study objective was to describe characteristics and utilization patterns of tirzepatide users with type 2 diabetes (T2D) using the Healthcare Integrated Research Database in the USA.

Methods

Adults (≥18 years) included had T2D diagnosis; ≥1 tirzepatide claim (May 2022–January 2023; first claim date = index date); and continuous medical and pharmacy enrollment during the 6-month baseline and follow-up periods from the index date. Baseline demographics, clinical characteristics, and 6-month follow-up dosing and treatment patterns were summarized descriptively.

Results

The study included 15,665 patients with T2D initiating tirzepatide (mean age: 53.2 years; 58.5% women; 76.7% non-Hispanic white). During the 6-month baseline period, hypertension (69.2%), dyslipidemia (69.2%), overweight/obesity (58.4%), and obstructive sleep apnea (22.8%) were commonly reported comorbidities. Over half of the patients (51.2%) had used glucagon-like peptide-1 (GLP-1) receptor agonist (RA) before initiating tirzepatide. The mean glycated hemoglobin (HbA1c) was 7.6% (n = 5175), and 58.4% of these patients had HbA1c ≥7%. The mean body mass index (BMI) was 38.7 kg/m² (n = 3459), and 87.8% of these patients either had Class 1, 2, or 3 obesity. Among patients with a single prescription on each fill date (N = 14,986), 84.1% initiated tirzepatide at ≤5 mg dose. During sixth prescription refill (n = 7304), 56.5% were receiving tirzepatide doses of <10 mg. During the 6-month follow-up period, 69.6% of patients had ≥1 dose escalation and 17.2% had ≥1 dose de-escalation. The mean time to first dose escalation was 59.1 days and first dose de-escalation was 104.8 days. Tirzepatide adherence (proportion of days covered [PDC] ≥80%) was 57.5% and persistence (45-day gap) was 73.3% at 6 months. Of patients who discontinued tirzepatide (n = 4177; 26.7%), 29.1% re-initiated tirzepatide (45-day gap).

Conclusion

Patients with T2D initiating tirzepatide had multimorbidity; uncontrolled diabetes; and mean BMI was consistent with Class 2 obesity. Patients showed favorable tirzepatide adherence and persistence profiles, and the majority remained at <10 mg doses during the 6-month follow-up period.

Plain Language Summary

Type 2 diabetes (T2D) is a growing health concern and is one of the leading causes of death and disability globally. Tirzepatide is recently approved in the USA for the treatment of T2D (May 2022) and obesity (November 2023). However, real-world data on use of tirzepatide are lacking given its relatively recent approval. We used large administrative claims database to describe characteristics of adult patients living with T2D in the USA who have started treatment with tirzepatide and understand treatment utilization patterns among these patients. The study results showed that patients starting on tirzepatide had high comorbidity burden, poorly controlled diabetes, and overweight/obesity. Additionally, over half of the patients had previously tried similar antidiabetic medications before beginning tirzepatide treatment. The study found that most patients start on a low dose of tirzepatide (2.5 mg or 5 mg). Six months after initiating tirzepatide, the majority of patients had increased their dosage but remained on doses less than 10 mg. A large proportion of patients were taking tirzepatide as prescribed and only a smaller group of patients discontinued tirzepatide treatment during the first 6 months. Future studies will be key to understanding long-term usage patterns and effectiveness of tirzepatide in managing T2D.

Key Summary Points

Why carry out this study?

Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) approved in the USA for treatment of type 2 diabetes (T2D; May 2022) and obesity (November 2023).

While tirzepatide has demonstrated efficacy versus placebo and active comparators in phase 3 SURPASS clinical trial program, real-world data on tirzepatide utilization in T2D are lacking considering its relatively recent availability.

We conducted a real-world retrospective cohort study using Healthcare Integrated Research Database to describe characteristics and utilization patterns of tirzepatide initiators with T2D in the USA.

What was learned from the study?

Findings from this real-world study suggest that patients with T2D initiating tirzepatide had uncontrolled diabetes; multimorbidity; and mean body mass index consistent with Class 2 obesity. Over half of the patients were GLP-1 RA–experienced.

During the 6-month follow-up period, the majority of the patients had at least one tirzepatide dose escalation, and remained on doses <10 mg at sixth prescription fill. Patients showed high treatment adherence and persistence at 6 months.

Future studies should focus on long-term follow-up among patients with T2D initiating tirzepatide to understand real-world treatment utilization patterns and effectiveness for better management of T2D.

Introduction

Type 2 diabetes (T2D) is a growing health concern worldwide and is one of the top 10 causes of death and disability globally [1, 2]. In the US adult population, the estimated prevalence of diabetes in 2021 was over 38 million, and 90–95% of these individuals had T2D [3]. Moreover, an estimated 8.7 million adults were still living with undiagnosed diabetes [3]. In 2022, the total estimated cost of diagnosed diabetes was $412.9 billion in the USA, with diabetes accounting for 1 in 4 healthcare dollars [4]. Additionally, increased medication expenditures, reduced employment due to disability, presenteeism, productivity loss, and diabetes-related complications have a profound impact on the financial well-being and quality of life in people with diabetes [4].

Despite expansion in the treatment armamentarium for T2D, only half (50.5%) of people with diabetes in the USA meet glycemic control targets, i.e., glycated hemoglobin level (HbA1c) of <7% [5]. Obesity plays a key role in the pathophysiology of diabetes and is a major risk factor for developing T2D and cardiorenal complications [6, 7]. The 2024 Standards of Care from American Diabetes Association (ADA) recommend having treatment goals that target both hyperglycemia and weight management in people with diabetes [6]. Thus, therapies that can improve glycemic control along with weight reduction can help achieve the overall T2D management goal of preventing diabetes-related complications [6, 8]. In addition, a holistic, patient-centric approach that takes into account demographic characteristics, social determinants of health (SDoH), and comorbidity burden is crucial for improving health outcomes in diabetes [1, 8, 9].

Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) approved in the USA for treatment of T2D (May 2022) [10] and obesity (November 2023) [11]. The phase 3 SURPASS clinical trial program evaluated the efficacy and safety of tirzepatide (5 mg, 10 mg, or 15 mg) alone or in combination with commonly prescribed antihyperglycemic medications (metformin, sodium-glucose cotransporter 2 [SGLT2] inhibitors, sulfonylureas, and insulin glargine) in patients with T2D. Tirzepatide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight versus placebo (SURPASS-1, SURPASS-5) [12, 13], and active comparators including semaglutide 1 mg (SURPASS-2) [14], titrated insulin degludec (SURPASS-3) [15], and titrated insulin glargine (SURPASS-4) [16]. Treatment with tirzepatide also resulted in significant improvements in health- and weight-related quality of life across the five SURPASS studies [17]. In the phase 3 SURMOUNT-2 trial in patients with obesity and T2D, treatment with tirzepatide resulted in clinically meaningful reduction in body weight and substantial reduction in HbA1c levels [18].

Evidence from meta-analyses and secondary analyses of clinical trials suggests that tirzepatide may improve other outcomes of interest for patients with T2D. Tirzepatide may reduce urine albumin-to-creatinine ratio and maintain renal function [19], improve levels of hepatic transaminases, and reduce liver fat content [20] versus placebo or active comparators. Preliminary evidence suggests no increased risk of cancer [21]. In a post hoc mediation analysis of the SURPASS program, tirzepatide was associated with reductions in systolic blood pressure across doses [22], while in a pre-specified meta-analysis of the SURPASS program, tirzepatide showed cardiovascular safety compared to controls [23].

Although tirzepatide has demonstrated efficacy in phase 3 clinical trials, real-world data on utilization of tirzepatide in T2D are limited given its relatively recent availability. The overall objective of this real-world retrospective study was to characterize the cohort initiating tirzepatide for T2D and to describe utilization patterns of tirzepatide in these patients using a large claims database in the USA.

Methods

Study Design and Population

This single arm, cross-sectional, retrospective, observational study was conducted using the Healthcare Integrated Research Database (HIRD^®) between 01 November 2021 and 31 July 2023 (study period).

The study included adult patients who had ≥1 claim for tirzepatide between 13 May 2022 and 31 January 2023 (patient identification period). Index date was the date of the first observed claim of tirzepatide during the patient identification period. Included patients had ≥2 distinct claims on different dates for T2D diagnosis (E11%) during all available pre-index period (October 2015 onwards), including the index date. Patients were required to have continuous medical and pharmacy enrollment (commercial or Medicare Advantage plans) during the baseline (6 months preceding the index date and excluding the index date) and follow-up (6 months following and including the index date) periods. Patients aged <18 years on the index date were excluded from the study.

Diagnoses and procedures for both outpatient and inpatient visits/stays were identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes; ICD-10 procedure coding system (ICD-10-PCS); Current Procedural Terminology; and Healthcare Financing Administration Common Procedure Coding System. Outpatient pharmacy claims were captured by National Drug Codes.

Ethical Approval

Researchers accessed data in the format of a limited dataset for which data use agreements were in place with the covered entities in compliance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule; therefore, institutional review board approval was not required.

Data Sources

The HIRD is curated by Carelon Research and is one of the largest US healthcare databases. It contains health-related claims information from commercially insured populations enrolled in traditional health maintenance organizations, preferred provider organizations, Medicare Advantage, and consumer-directed health plans. The claims data are integrated across data sources, including outpatient laboratory test orders and results, electronic health records (EHR), race and ethnicity data, and SDoH data [24]. The 2020 HIRD population (commercial and managed Medicare) is representative of the 2020 US Census population in terms of sex, age, and geographic region of residence; the race/ethnicity distribution indicates slightly more non-Hispanic white members compared to the Census [25].

The study used SDoH data from the 2019 American Community Survey (ACS) at the Census block group level [26], and member-level race and ethnicity data sourced from enrollment files, EHR, and imputation algorithms. Additionally, area-level data from the Food Access Research Atlas (FARA; 2019) developed by the Economic Research Service, US Department of Agriculture [27], and individual-level urbanicity data derived from the National Center for Health Statistics (NCHS; 2013) [28] were included.

Baseline Patient Characteristics

Demographics and Socioeconomic Characteristics

Baseline demographics were assessed on the index date and included age, sex, region, payor type, health plan type, and race/ethnicity (using member-level HIRD data). SDoH data were reported at the neighborhood level, based on patient residence on index date. Variables included quartiles of the socioeconomic status (SES) index score (from 1 being least advantaged to 4 being most advantaged, using national data as the benchmark); unemployment; education; income; residence area (rural, urban, or suburban areas; reported from NCHS data); and low income, low food access area (living more than 1 mile [urban area] or more than 10 miles [rural area] from the nearest supermarket; derived from FARA).

Clinical Characteristics

Comorbidities of interest and adapted Diabetes Complication Severity Index (aDCSI) categories were assessed during the 6-month baseline period. Tirzepatide-prescribing provider specialty (primary care physician, non-physician clinician, endocrinologist, cardiologist, others) was captured on the index date. Use of antihyperglycemic, antihypertensive, antihyperlipidemic, anti-obesity, and antidepressant medications in the baseline period was assessed. For antihyperglycemic medications, proportion of patients on different classes of antihyperglycemic medications, type of insulin used, the last prescribed GLP-1 RA, and the last prescribed dose for GLP-1 RA before the index date were also reported.

Among patients with available clinical measures, HbA1c levels; HbA1c categories (≥7%, 7% to <8%, 8% to <9%, ≥9%); body mass index (BMI); BMI categories (underweight, normal weight, overweight, and Class 1 to Class 3 obesity); and weight were assessed during a pre-defined baseline assessment window (‘index date − 90 days’ to ‘index date + 14 days’).

Tirzepatide Utilization Patterns

Dosing Patterns

The mean number of tirzepatide prescription refills was calculated based on the total number of unique, paid prescription claims of tirzepatide per patient during the 6-month follow-up period. The number of patients who filled tirzepatide prescription for the second, third, and fourth time after the index fill, and the mean time between the index and second fill were also assessed. Tirzepatide dose transitions for the first six prescription refills (excluding patients with multiple fills per day) were illustrated via a Sankey diagram starting from the index dose to the last recorded dose for each patient. Specific dose escalation and de-escalation patterns were also assessed during the 6-month follow-up period.

Treatment Patterns

Adherence was measured using proportion of days covered (PDC): number of days with tirzepatide on-hand divided by length of the follow-up period. A patient with PDC ≥ 80% was defined as “adherent”. Persistence was defined as the number of days of continuous therapy from the point of tirzepatide initiation until the end of the follow-up period, allowing for a maximum gap of 45 days between prescription refills. Discontinuation date was the date of last prescription refill in the continuous treatment segment plus days’ supply of that refill. The analysis assumed that there was no tirzepatide stockpiling. Among the patients who discontinued tirzepatide, the proportion of patients who re-initiated tirzepatide after the 45-day gap was assessed. A sensitivity analysis using 60-day gap was performed for persistence/discontinuation and re-initiation after discontinuation.

Statistical Analyses

Baseline demographic and clinical characteristics of the cohort initiating tirzepatide and 6-month follow-up tirzepatide dosing and treatment patterns were summarized descriptively. Continuous variables were presented as mean and standard deviation (SD) and/or median, interquartile range (IQR), and minimum and maximum values. Categorical variables were summarized as frequencies and percentages. No hypotheses testing was conducted. We utilized imputation methods to manage missing data for measures such as days’ supply. Analyses were conducted using a combination of the Instant Health Data platform (Panalgo, Boston, MA); R, version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria); and Statistical Analysis Software (SAS) Enterprise Guide, version 9.3 (SAS Institute Inc., Cary, NC, USA).

Results

Baseline Patient Characteristics

Demographics and Socioeconomic Characteristics

A total of 15,665 patients initiating tirzepatide for T2D were included in the study (Fig. 1). The mean (SD) age at index was 53.2 (10.0) years and the majority of patients were 45 to 64 years old (71.0%). The proportion of women was 58.5% and that of non-Hispanic white patients was 76.7%. Overall, 47.4% of patients were from the US South region. Most patients (92.2%) were insured under a commercial plan (Table 1).

Fig. 1.

Patient attrition

Table 1.

Baseline demographic and socioeconomic characteristics of patients with T2D initiating tirzepatide

Variables	Patients initiating tirzepatide (N = 15,665)
Demographic characteristics on index date
Age (years), mean (SD)	53.2 (10.0)
Age categories (years), n (%)
18–44	2981 (19.0)
45–64	11,056 (71.0)
65–74	1379 (8.8)
≥75	249 (1.6)
Womena, n (%)	9168 (58.5)
Geographic region, n (%)
Northeast	1605 (10.3)
Midwest	4123 (26.3)
South	7427 (47.4)
West	2510 (16.0)
Payor type, n (%)
Commercial	14,444 (92.2)
Medicare advantage	1136 (7.3)
Medicare supplement and Part D	85 (0.5)
Health plan typea, n (%)
Health Maintenance Organization (HMO)	2660 (17.0)
Preferred Provider Organization (PPO)	9246 (59.1)
Consumer-Driven Health Plan (CDHP)	3736 (23.9)
Race/ethnicity with available data, n (%)	14,174 (90.5)
White, not Hispanic or Latino	10,867 (76.7)
Black or African American, not Hispanic or Latino	1347 (9.5)
Hispanic or Latino of any race	1334 (9.4)
Asian, not Hispanic or Latino	357 (2.5)
American Indian or Alaska Native, not Hispanic or Latino	68 (0.5)
Other race, not Hispanic or Latino	201 (1.4)
Area-level SDoH data from the 2019 ACS
Patients with area-level SDoH data available, n (%)	14,744 (94.1)
Quartiles of SES index scoreb, n (%)	14,702 (93.9)
1	2930 (19.9)
2	3959 (26.9)
3	4093 (27.8)
4	3720 (25.3)
Patients with area-level employment data available, n (%)	14,742 (94.1)
Percentage of population that was unemployed, mean (SD)	5.2 (5.0)
Patients with area-level education data available, n (%)	14,743 (94.1)
Percentage of population aged ≥ 25 years old who had:
High school diploma or equivalent (but not above), mean (SD)	28.8 (12.7)
Completed at least 4 years of college, mean (SD)	30.1 (19.2)
<9 years of education, mean (SD)	4.5 (6.1)
High school-equivalent degree (GED), mean (SD)	4.5 (4.0)
Patients with area-level income data available, n (%)	14,209 (90.7)
Median family income in the prior 12-month period (USD), mean (SD)	84,707.1 (39,338.2)
Patients with area-level income level data available, n (%)	14,743 (94.1)
Percentage of families with income below the poverty line, mean (SD)	12.3 (11.4)
Percentage of households receiving public assistance in the past 12 months (cash payment only), mean (SD)	2.0 (3.3)
Percentage of households receiving supplemental security income, mean (SD)	5.4 (5.6)
Patients with residence area (NCHS) data available, n (%)	14,744 (94.1)
Urban	7651 (51.9)
Suburban	3825 (25.9)
Rural	3268 (22.2)
Patients with food access (FARA) data available, n (%)	14,743 (94.1)
Low income, low food access area	1875 (12.7)

ACS, American Community Survey; FARA, Food Access Research Atlas; GED, general education diploma; NCHS, National Center for Health Statistics; SD, standard deviation; SDoH, social determinants of health; SES, socioeconomic status; T2D, type 2 diabetes; USD, United States dollars

^aOther patients have missing information <0.3%

^bThe SES index is a composite SDoH measure based on seven factors (unemployment rate, poverty rate, median household income, median home value, proportion of participants not having a high school degree, proportion of participants with a college degree, proportion of households that average one or more persons per room [crowding]). The SES index score is reported in quartiles, with “4” indicating a patient is in the top 25% of the SES index score (i.e., most advantaged SES group) and “1” indicating a patient is in the bottom 25% of the SES index score (i.e., least advantaged SES group), using national data as the benchmark

Area-level SDoH data were available for >90% of patients. Approximately 19.9% of patients had an SES index score of 1 (least advantaged), indicating slightly higher SES in this patient sample compared to the US national population. Patients in this study resided in areas with a mean (SD) unemployment rate of 5.2% (5.0) and mean (SD) proportion of the population with at least 4 years of college of 30.1% (19.2). Over half of the patients (51.9%) were living in urban areas and 12.7% of patients were from low income, low food access areas (Table 1).

Clinical Characteristics

During the 6-month baseline period, the most frequently reported comorbidities were hypertension (69.2%), dyslipidemia (69.2%), overweight or obesity (58.4%), and obstructive sleep apnea (22.8%). The mean (SD) aDCSI score was 0.9 (1.3) and the commonly reported aDCSI categories were neuropathy (19.5%), cardiovascular complication (14.5%), and nephropathy (11.3%) (Table 2).

Table 2.

Clinical and provider characteristics in patients with T2D initiating tirzepatide

Variables	Patients initiating tirzepatide (N = 15,665)
Clinical characteristics during 6-month baseline period
Comorbidities of interesta, n (%)
Hypertension	10,846 (69.2)
Dyslipidemia	10,842 (69.2)
Overweight or obesity	9141 (58.4)
Obstructive sleep apnea	3572 (22.8)
Anxiety	3016 (19.3)
Depression	2648 (16.9)
Osteoarthritis	2209 (14.1)
Osteoarthritis—knee	981 (6.3)
Adapted Diabetes Complication Severity Index (aDCSI) score (range 0–13), mean (SD)	0.9 (1.30)
aDCSI complication categoryb, n (%)
Neuropathy	3061 (19.5)
Cardiovascular complication	2277 (14.5)
Nephropathy	1775 (11.3)
Peripheral vascular disease	1563 (10.0)
Retinopathy	1327 (8.5)
Provider characteristics on index date
Prescribing physician specialty associated with index tirzepatide claimc, n (%)
Primary care physician (PCP)d	5687 (36.3)
Non-physician clinician (NPC)e	5466 (34.9)
Endocrinologist	3388 (21.6)
Cardiologist	115 (0.7)
Otherf	847 (5.4)
Unknown/missing	162 (1.0)

IQR, interquartile range; min, minimum; max, maximum; SD, standard deviation; T2D, type 2 diabetes

^aPatients who had a diagnosis claim for selected comorbidities before 6-month baseline period but not later are not captured. Less than 5% of patients had congestive heart failure, a history of bariatric surgery, myocardial infarction, or non-alcoholic steatohepatitis

^bLess than 2% of patients had metabolic disorder or cerebrovascular complication

^cThe denominator is the number of total tirzepatide-treated patients

^dPCP includes general/family practice, internal medicine, geriatric medicine, osteopathic medicine, and pediatric medicine specialties

^eNon-physician clinician includes nurse practitioner, physician assistant, and similar occupations

^fOther includes additional medical specialties rarely observed

The first prescription for tirzepatide was commonly prescribed by primary care physicians (36.3%), non-physician clinicians (34.9%), and endocrinologists (21.6%) (Table 2).

Prior to initiating tirzepatide, 88.3% patients (n = 13,835) were prescribed antihyperglycemic medications, with the majority receiving either monotherapy (42.6%) or dual therapy (41.9%). Baseline use of non-GLP-1 oral antihyperglycemic medication was seen in 74.0% (n = 11,595) of patients, and metformin (80.6%) was the most frequently prescribed medication among these patients. Other prescribed non-GLP-1 oral antihyperglycemic medications included sulfonylureas (21.5%), dipeptidyl peptidase 4 (DPP4) inhibitors (9.6%), SGLT2 inhibitors (41.6%), and thiazolidinediones (7.8%). Insulin was prescribed to 27.5% (n = 4311) of patients; of these, 83.4% were receiving long-acting insulin. More than half of the patients (51.2%; n = 8013) had received GLP-1 RA during the 6-month baseline period before initiating tirzepatide; injectable semaglutide (45.4%; n = 3634) and dulaglutide (40.9%; n = 3281) were frequently prescribed as the last GLP-1 RAs among these patients. For injectable semaglutide (n = 3634), the commonly prescribed last dose was 1 mg (47.7%), followed by 0.25 mg or 0.5 mg (32.2%), and 2 mg (20.3%). The last prescribed doses for dulaglutide (n = 3281) were 1.5 mg (30.5%), 4.5 mg (28.9%), 3 mg (26.8%), and 0.75 mg (14.1%) per 0.5 mL. Other medication use included antihypertensives (74.8%), antihyperlipidemics/dyslipidemics (66.2%), and antidepressants (36.6%) (Table 3).

Table 3.

Medication utilization during 6-month baseline period in patients with T2D initiating tirzepatide

Variables	Patients initiating tirzepatide (N = 15,665)
Patients with ≥1 fill of antihyperglycemic medications, n (%)	13,835 (88.3)
Monotherapy	5893 (42.6)
Metformin only	2019 (14.6)
Dual therapy	5800 (41.9)
Triple therapy	2142 (15.5)
Patients with ≥1 non-GLP-1 oral antihyperglycemic fill, n (%)	11,595 (74.0)
Metformin, alone or fixed dose combination pill	9341 (80.6)
Sulfonylureas, alone or fixed dose combination pill	2492 (21.5)
DPP4 inhibitors, alone or fixed dose combination pill	1116 (9.6)
SGLT2 inhibitors, alone or fixed dose combination pill	4825 (41.6)
Thiazolidinediones, alone or fixed dose combination pill	908 (7.8)
Patients with ≥1 insulin filla, n (%)	4311 (27.5)
Rapid/ultra-rapid actingb	1951 (45.3)
Short actingc	80 (1.9)
Intermediate actingd	63 (1.5)
Long actinge	3594 (83.4)
Premixf	199 (4.6)
Patients with ≥1 GLP-1 RA fill, n (%)	8013 (51.2)
Last GLP-1 RA prescription utilization by productg, n (%)
Dulaglutide (Trulicity®)	3281 (40.9)
Oral semaglutide (Rybelsus®)	476 (5.9)
Injectable semaglutide (Ozempic®)	3634 (45.4)
Exenatide Bcise (Bydureon Bcise®)	113 (1.4)
Exenatide BID (Byetta®)	10 (0.1)
Liraglutide (Victoza®)	408 (5.1)
GLP-1 RA/insulin combination	98 (1.2)
Last GLP-1 RA prescription dosingh, n (%)
Dulaglutide (Trulicity®)	n = 3281 (40.9)
0.75 mg/0.5 mL	464 (14.1)
1.5 mg/0.5 mL	1001 (30.5)
3 mg/0.5 mL	879 (26.8)
4.5 mg/0.5 mL	947 (28.9)
Oral semaglutide (Rybelsus®)	n = 476 (5.9)
3 mg	69 (14.5)
7 mg	168 (35.3)
14 mg	239 (50.2)
Injectable semaglutide (Ozempic®)	n = 3634 (45.4)
0.25 mg or 0.5 mg	1170 (32.2)
1 mg	1734 (47.7)
2 mg	737 (20.3)
Patients with ≥1 antihypertensive medication fill, n (%)	11,715 (74.8)
Patients with ≥1 antihyperlipidemic/dyslipidemic medication fill, n (%)	10,373 (66.2)
Patients with ≥1 anti-obesity medication fill, n (%)	476 (3.0)
Patients with ≥1 antidepressant medication fill, n (%)	3643 (36.6)

None of the medication categories are mutually exclusive except the mono, dual, and triple therapy

BID, twice a day; DPP4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide-1; RA, receptor agonist; QW, once weekly; SGLT2, sodium-glucose cotransporter 2

^aInsulin includes rapid-acting, short-acting, intermediate-acting, long-acting, and premix insulins

^bRapid-acting insulins: Insulin aspart (Fiasp^®, Novolog^®), insulin glulisine (Apidra^®), insulin lispro (Admelog^®, Humalog^®, Lyumjev^®), inhaled-insulin (Afrezza^®), other insulin (Myxredlin^®)

^cShort-acting insulin: Human Regular (Humulin R^®, Novolin R^®, Velosulin R^®, ReliOn R^®)

^dIntermediate-acting insulin: NPH (Humulin N^®, Novolin N^®, ReliOn N^®)

^eLong-acting insulin: Glargine (Lantus^®, Toujeo^®, and Basaglar^®), detemir (Levemir^®), degludec (Tresiba^®), U500

^fPremix: Humalog Mix75/25^®, Humalog Mix 50/50^®, Humalin 70/30^®, Novolin 70/30^®, Novolog 70/30^®, Novolog Mix 50/50^®, Ryzodeg 70/30^®, Humulin 50/50^®, ReliOn 70/30^®

^gUse of following drugs was not reported: exenatide QW vial/syringe (Bydureon^®); exenatide QW pen (Bydureon^®); lixisenatide (Adlyxin^®); albiglutide (Tanzeum^®)

^hLast prescribed dose was not mutually exclusive

In patients with a valid HbA1c value available from labs and EHR (n = 5175 or 33.0%), the mean (SD) HbA1c level during the pre-defined baseline assessment window was 7.6% (1.8) and 58.4% of these patients reported HbA1c ≥7%. A total of 3459 patients (22.1%) had a valid BMI measurement and the mean (SD) BMI of these patients was 38.7 (8.3) kg/m². Of these 3459 patients, 24.1% had Class 1 obesity, 24.2% had Class 2 obesity, and 39.5% had  Class 3 obesity. Valid weight data were available for 3680 patients (23.5%) and the mean (SD) weight of these patients was 112.4 (27.0) kg (Table 4).

Table 4.

Clinical measurements during pre-defined baseline window^a in patients with T2D initiating tirzepatide

Variable	Patients initiating tirzepatide (N = 15,665)
HbA1c measurement results
Patients with ≥1 valid HbA1c test claim, n (%)	11,515 (73.5)
Patients with ≥1 valid HbA1c value from labs and EHR, n (%)	5175 (33.0)
HbA1c (%)b
Mean (SD)	7.6 (1.8)
Median (IQR)	7.2 (6.4–8.5)
HbA1c categoriesb, n (%)
≥7%	3022 (58.4)
7% to <8%	1278 (24.7)
8% to <9%	760 (14.7)
≥9%	984 (19.0)
BMI measurement results
Patients with ≥1 valid BMI value, n (%)	3459 (22.1)
BMIb (kg/m2)
Mean (SD)	38.7 (8.3)
Median (IQR)	37.7 (32.8–43.3)
BMI categoriesb (kg/m2), n (%)
Overweight: ≥25 to <30	364 (10.5)
Class 1 obesity: ≥30 to <35	834 (24.1)
Class 2 obesity: ≥35 to <40	838 (24.2)
Class 3 obesity: ≥40	1365 (39.5)
Weight measurement results
Patients with ≥1 valid weight record, n (%)	3680 (23.5)
Weightb (kg)
Mean (SD)	112.4 (27.0)
Median (IQR)	108.9 (93.4–128.3)

^aThe pre-defined baseline window had an outer boundary of ‘index date − 90 days’ and inner boundary of ‘index date + 14 days’

BMI, body mass index; EHR, electronic health record; HbA1c, glycated hemoglobin; IQR, interquartile range; min, minimum; max, maximum; SD, standard deviation

^bReporting value closest to the index date. Of patients with ≥1 valid BMI value, 6 (0.2%) were underweight (BMI <18.5 kg/m²) and 52 (1.5%) had a normal weight (BMI ≥18.5 to <25 kg/m²)

Tirzepatide Utilization Patterns

Dosing Patterns

In the overall population (n = 15,665), the mean (SD) number of tirzepatide prescription fills was 5.2 (2.2) during the 6-month follow-up period. A total of 92.6% (n = 14,507) of patients had a second prescription fill, 84.8% (n = 13,282) had a third, and 74.1% (n = 11,615) had a fourth prescription fill. The mean (SD) days between first and second fills was 37.8 (24.8) days.

Of the overall patient population (N = 15,665), 95.7% (n = 14,986) patients had a single prescription refill on each fill date; a Sankey diagram showing dosing patterns for the first six prescription fills among these patients is depicted in Fig. 2. During the index fill, most patients initiated tirzepatide at 2.5 mg (43.2%) or 5 mg (40.9%) dose. At sixth prescription refill (n = 7304), 6.2% patients were still receiving tirzepatide dose of 2.5 mg and over half of the patients were receiving tirzepatide doses of 5 mg (26.5%) or 7.5 mg (23.9%). The proportions of patients receiving higher tirzepatide doses at sixth prescription refill were 20.2% for 10 mg; 11.0% for 12.5 mg; and 12.3% for 15 mg.

Fig. 2.

Sankey diagram* showing tirzepatide dosing patterns for first six prescription fills in patients with T2D (excluding patients with multiple tirzepatide fills on a single day). *Sankey analysis describes dosing patterns using the observed number of fills over the 6-month follow-up period regardless of days’ supply or potential gaps between fills. Patients who interrupt and restart during the 6-month follow-up are included. T2D type 2 diabetes

Dose escalation and de-escalation patterns among patients who had a single prescription refill on each fill date (n = 14,986) are depicted in Fig. 3. During the 6-month follow-up period, 69.6% (n = 10,430) of patients had ≥1 dose escalation and the mean (SD) time to first dose escalation was 59.1 (40.9) days. Among patients who had a tirzepatide dose escalation (n = 10,430), more than half (55.7%) had first dose escalation during the second prescription refill (Fig. 3A). Most patients escalated tirzepatide dose from 2.5 mg to 5 mg (46.9%) or from 5 mg to 7.5 mg (51.8%) (Fig. 3B). Fewer patients (17.2%; n = 2571) had ≥1 dose de-escalation during the 6-month follow-up period and the mean (SD) time to first dose de-escalation was 104.8 (49.7) days. Of these patients (n = 2571), a majority (71.8%) had their first dose de-escalation between the third to sixth prescription refills (third, 18.3%; fourth, 20.0%; fifth, 18.1%; sixth, 15.5%) (Fig. 3A). Over half of the patients had tirzepatide dose de-escalation from 7.5 mg to 5 mg (28.6%) or from 5 mg to 2.5 mg (21.6%) (Fig. 3C).

Fig. 3.

Escalation and de-escalation patterns during the 6-month follow-up period in patients with T2D initiating tirzepatide. T2D type 2 diabetes

Treatment Patterns

Overall, tirzepatide adherence (PDC ≥80%) was 57.5% and persistence was 73.3% (45-day gap) at 6 months (Table 5). The mean (SD) PDC was 0.8 (0.2). Overall, 26.7% of patients (n = 4177) discontinued tirzepatide using the 45-day gap criterion; the mean (SD) time from index date to discontinuation was 64.7 (35.3) days. Among the patients who discontinued tirzepatide, 29.1% re-initiated tirzepatide after the 45-day gap; the median (IQR) time to re-initiation was 65.0 (55.0–85.0) days (Table 5).

Table 5.

Adherence and persistence during the 6-month follow-up period in patients with T2D initiating tirzepatide

Variables	Patients initiating tirzepatide (N = 15,665)
Adherence (measured as PDC)
Mean (SD)	0.8 (0.2)
Median (IQR)	0.8 (0.6–0.9)
Min–max	0.1–1.0
PDC categories, n (%)
PDC ≥80%	9000 (57.5)
PDC ≥90%	5623 (35.9)
Persistence/discontinuation (45-day gap between refills)
Patients who were persistent, n (%)	11,487 (73.3)
Patients who discontinue, n (%)	4177 (26.7)
Days from index date to discontinuationa
Mean (SD)	64.7 (35.3)
Median (IQR)	59.0 (28.0–90.0)
Min–max	1.0–137.0
Number of patients who re-initiated tirzepatide, n (%)	1215 (29.1)
Days from tirzepatide discontinuation to re-initiation
Mean (SD)	72.7 (23.6)
Median (IQR)	65.0 (55.0–85.0)
Min–max	47.0–163.0
Persistence/discontinuation (60-day gap between fills)
Patients who were persistent, n (%)	12,264 (78.3)
Patients who discontinue, n (%)	3401 (21.7)
Days from index date to discontinuationa
Mean (SD)	59.9 (31.4)
Median (IQR)	56.0 (28.0–84.0)
Min–max	7.0–122.0
Number of patients who re-initiated tirzepatide, n (%)	692 (20.3)
Days from tirzepatide discontinuation to re-initiation
Mean (SD)	87.2 (21.8)
Median (IQR)	82.0 (70.0–98.0)
Min–max	62.0–163.0

IQR, interquartile range; min, minimum; max, maximum; PDC, proportion of days covered; SD, standard deviation; T2D, type 2 diabetes

^aTime of discontinuation is defined as the last fill date in the continuous treatment segment plus days’ supply of that fill

The sensitivity analysis using a 60-day gap showed a higher persistence (78.3%; n = 12,264) and a lower discontinuation rate (21.7%; n = 3401) (Table 5). The mean (SD) time from index date to discontinuation was 59.9 (31.4) days. Among the patients who discontinued, 20.3% re-initiated tirzepatide after the 60-day gap; the median (IQR) time to re-initiation was 82.0 (70.0–98.0) days (Table 5).

Discussion

This retrospective study described real-world patient characteristics and treatment utilization patterns in patients with T2D initiating tirzepatide in the USA using administrative claims database. Baseline patient characteristics were largely consistent with GLP-1 RA real-world studies [29–33]. Hypertension, dyslipidemia, overweight/obesity, and obstructive sleep apnea were frequently reported comorbidities in patients with T2D; and neuropathy was the most frequently reported diabetes complication. Prior to initiating tirzepatide, more than half of the patients used GLP-1 RAs in the previous 6 months. The mean BMI of patients initiating tirzepatide was consistent with Class 2 obesity and approximately three in five patients had uncontrolled diabetes (HbA1c ≥7%, 58.4%) at baseline. During the 6-month follow-up period, the most commonly prescribed maximum tirzepatide dose was 5 mg, and the majority of the patients had at least one dose escalation. Patients initiating tirzepatide showed high treatment adherence and persistence during the first 6 months of treatment.

While most patients in this study had commercial insurance, 19.9% of patients lived in neighborhoods with unmet social needs. This is consistent with recent findings from the literature and emphasizes the importance of screening all patients for health-related social needs [34–38]. Unfavorable social determinants are associated with higher prevalence of T2D and obesity [39], poor glycemic control, and twofold increased risk of mortality in patients with T2D [38]. Treatment non-adherence is often due to low socioeconomic status, limited health literacy, and food insecurity. Patients with access to quality healthcare services and a supportive social environment are more likely to adhere to treatment plans [35, 40–42]. Thus, incorporating SDoH is critical to a patient-centric approach for T2D management and for achieving health equity in patients with T2D.

Obesity is a major risk factor for the increasing prevalence of diabetes [1]. In this study, based on the ICD coding, approximately 60% of patients with T2D initiating tirzepatide had obesity or overweight. Since diagnosis of obesity and overweight is still not optimally captured in administrative claims databases, this is likely an under-representation of comorbid obesity in patients with T2D. However, among those with recorded BMI, 98% were classified as having overweight or obesity. This high prevalence of obesity among patients with T2D underscores the importance of treating comorbid obesity. The recent ADA 2024 recommendations [6] suggest that patients with T2D may benefit from treatment that not only improves glycemic control but also helps achieve weight management goals. Moreover, weight loss enhances the overall quality of life and improves factors linked to heart and metabolic health, thus contributing positively to comprehensive health improvement [43].

The recommended tirzepatide starting dosage for T2D is 2.5 mg injected subcutaneously once weekly for 4 weeks, followed by 5 mg once weekly. If additional glycemic control is needed, it is recommended to increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose to a maximum dosage of 15 mg [44]. Consistent with the dosing recommendations, 43.2% of patients initiated tirzepatide treatment with 2.5 mg dose. More than half of the patients were receiving doses <10 mg at the sixth prescription refill and tirzepatide 5 mg was the most commonly prescribed maximum dose. Additionally, the mean time to first dose escalation was greater than 4 weeks (approximately 59 days). This suggests that dose escalation to the clinically more effective doses (5 mg, 10 mg, or 15 mg) in the real world is more gradual compared to that performed in clinical trials. The longer time to dose escalation may be based on patients’ HbA1c levels, tolerability concerns, or could be potentially explained by therapeutic inertia (the failure to initiate or intensify treatment in a timely manner) [45]. Moreover, achievement of desired glycemic targets and weight reduction at low doses, prescriber preferences, and access and supply issues [46] may inform dose escalation strategies in the real world. The current study did not assess glycemic outcomes longitudinally at each dose and hence it is not possible to assess if the dose escalation patterns were optimal for glycemic outcomes.

In this study, tirzepatide persistence (73.3%) using a 45-day treatment gap was similar to that of dulaglutide (69.2%–71.9%) and greater than that of semaglutide (59.2%–62.2%) at 6 months reported previously in claims-based studies in patients with T2D newly initiating GLP-1 therapy [47, 48]. Similarly, the 6-month tirzepatide adherence rate (57.5%) was similar to that of dulaglutide (58%–63.4%) and greater than that of semaglutide (42.7%–47.8%) reported in these studies [47, 48]. In people with T2D, greater medication adherence and persistence are associated with improved glycemic control, lower risk of diabetes complications, and improved economic outcomes [48, 49]. Future studies should focus on evaluating comparative adherence and persistence for tirzepatide versus other GLP-1 RAs.

The study findings should be interpreted considering several limitations. Our study used data from commercially insured patients that may not be representative of all patients with T2D. The requirement of 6-month continuous enrollment during the 6-month pre-index and follow-up periods may limit the generalizability of outcomes for patients who disenrolled within 6 months after the first observed tirzepatide-related claim. This can create selection bias, and our single-cohort study may exclude patients with different health trajectories and shorter follow-up times, affecting the representativeness of the study population. The study findings should be interpreted considering the caveats commonly associated with administrative database analyses, including potential coding errors and incomplete data. Coding errors could result in under- or overestimation of outcomes like comorbidities and adherence. Incomplete data, especially for HbA1c, weight, and BMI measurements available for only a subset of patients, could impact the generalizability of these findings and bias the results toward patients with more comprehensive records. During the study period, tirzepatide supply shortages could have impacted the dosing, and escalation and de-escalation patterns, and should therefore be considered when interpreting the findings [46].

Conclusion

This real-world study found that patients with T2D initiating tirzepatide had multimorbidity; uncontrolled diabetes; and mean BMI consistent with Class 2 obesity. More than half of the patients were GLP-1 RA–experienced. The majority of the patients had at least one dose escalation, and were receiving doses <10 mg at sixth prescription fill. Patients with T2D initiating tirzepatide showed high treatment adherence and persistence during the 6-month follow-up period. Additionally, long-term follow-up studies evaluating dosing, treatment patterns, and real-world effectiveness among patients with T2D initiating tirzepatide could help in optimal use of antihyperglycemic treatment for better management of T2D.

Author Contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Reema Mody: Conception and design of the work, interpretation of data for the work, and critical review of the work for important intellectual content. Karishma Desai: Design of the work, acquisition and interpretation of data for the work, and critical review of the work for important intellectual content. Chia-Chen Teng: Acquisition, analysis and interpretation of data for the work, and critical review of the work for important intellectual content. Gally Reznor: Analysis of data for the work and critical review of the work for important intellectual content. Grace Stockbower: Conception of the work and critical review of the work for important intellectual content. Michael Grabner: Design of the work, acquisition and interpretation of data for the work, and critical review of the work for important intellectual content. Brian D. Benneyworth: Conception and design of the work, interpretation of data for the work, and critical review of the work for important intellectual content.

Funding

The study and all support for the manuscript, including the journal’s Rapid Service Fee, was funded by Eli Lilly and Company, Indianapolis, United States.

Data Availability

The data that support the findings of this study are available from Carelon Research, but restrictions apply to the availability of these data to external sources, and therefore they are not publicly available. Data may be made available through the corresponding author upon reasonable request and with permission of Carelon Research.

Declarations

Conflict of Interest

Reema Mody: Employment and stockholder, Eli Lilly and Company. Karishma Desai: Employment, Carelon Research; shareholder, Elevance Health. Chia-Chen Teng: Employment, Carelon Research; shareholder, Elevance Health. Gally Reznor: Former employment, Carelon Research. Work related to the study was performed during her tenure at Carelon Research. Grace Stockbower: Employment, Carelon Research. Michael Grabner: Employment, Carelon Research; shareholder, Elevance Health. Brian D. Benneyworth: Employment and stockholder, Eli Lilly and Company.

Ethical Approval

Researchers accessed data in the format of a limited dataset for which data use agreements were in place with the covered entities in compliance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule; therefore, institutional review board approval was not required.